@article{7f2b4da6ad8445798fd3407d6e73f5f6,
title = "High-potency ligands for DREADD imaging and activation in rodents and monkeys",
abstract = "Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are a popular chemogenetic technology for manipulation of neuronal activity in uninstrumented awake animals with potential for human applications as well. The prototypical DREADD agonist clozapine N-oxide (CNO) lacks brain entry and converts to clozapine, making it difficult to apply in basic and translational applications. Here we report the development of two novel DREADD agonists, JHU37152 and JHU37160, and the first dedicated 18F positron emission tomography (PET) DREADD radiotracer, [18F]JHU37107. We show that JHU37152 and JHU37160 exhibit high in vivo DREADD potency. [18F]JHU37107 combined with PET allows for DREADD detection in locally-targeted neurons, and at their long-range projections, enabling noninvasive and longitudinal neuronal projection mapping.",
author = "Jordi Bonaventura and Eldridge, {Mark A.G.} and Feng Hu and Gomez, {Juan L.} and Marta Sanchez-Soto and Abramyan, {Ara M.} and Sherry Lam and Boehm, {Matthew A.} and Christina Ruiz and Farrell, {Mitchell R.} and Andrea Moreno and {Galal Faress}, {Islam Mustafa} and Niels Andersen and Lin, {John Y.} and Ruin Moaddel and Morris, {Patrick J.} and Lei Shi and Sibley, {David R.} and Mahler, {Stephen V.} and Sadegh Nabavi and Pomper, {Martin G.} and Antonello Bonci and Horti, {Andrew G.} and Richmond, {Barry J.} and Michael Michaelides",
note = "Funding Information: This work was supported by the NIDA (ZIA000069), NIMH (ZIAMH002793, ZIAMH002795), NIA, and NINDS Intramural Research Programs, the NIA (R21AG054802) to A.G.H., the NIBIB (P41EB024495) to M.G.P. and by a European Research Council (ERC) 679714 STC grant to S.N. and Lundbeck Foundation fellowship R264-2017-3189 to A.M. We thank Takafumi Minamimoto and Yuji Nagai for consultation on how to establish PET imaging of DREADD expression in rhesus monkeys at the NIH, and for validation of initial results. We thank NIMH{\textquoteright}s Molecular Imaging Branch (Chief, Robert Innis) for imaging the monkeys: Robert Gladding and Jeih-San Liow for assistance with camera operation and data acquisition, Sanjay Telu and Victor Pike for radiochemical synthesis and Sami Zoghbi and Michael Frankland for radio-metabolite analysis. We thank Marisela Morales, Amy Newman, and Sergi Ferr{\'e} for access to instrumentation, Hirsch Davis for access to pharmacological screening resources and Jian Jin for providing C13, C21, and C22. We thank Robert Dannals, Polina Sysa-Shah, James Engles, Nancy Ator, Taek-Soo Lee, Ben Tsui, and Peter Koncz for access to resources and technical support. We also thank Alex Cummins for assistance with macaque tissue preparation, Walter Lerchner and Violette der Minassian for lentivirus production, J. Megan Fredericks, Janita Turchi and Jalene Shim for compound formulation and administration, and Michael Frankland for assistance with blood sampling. Publisher Copyright: {\textcopyright} 2019, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.",
year = "2019",
month = dec,
day = "1",
doi = "10.1038/s41467-019-12236-z",
language = "English (US)",
volume = "10",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}